This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Decreased contralateral breast cancer (BC) seen with aromatase inhibitor therapy suggests they may be effective for BC prevention. Nutriceuticals are popular alternatives for women who prefer dietary supplements over standard pharmaceuticals. Our group demonstrated a previously unknown anti-aromatase effect with grape-seed extract (GSE). We propose translation to a human BC chemoprevention trial. Objectives: 1. to determine whether GSE significantly suppresses circulating estrogens in postmenopausal women at increased BC risk, 2. to gather preliminary dose information, 3. to determine bioavailability, and 4. to evaluate safety and tolerability in humans. Methods: Twenty-four subjects will be treated with GSE at four dose levels for a 12-week period, following a 2-week placebo control period. Blood will be drawn at scheduled intervals for serum estrogen, procyanidin concentration, and aromatase inhibition assays. Markers of bone metabolism and adrenal suppression will be checked pre and post GSE, and symptom logs will be followed.